239 research outputs found
R-Ras regulates ÎČ1-integrin trafficking via effects on membrane ruffling and endocytosis
<p>Abstract</p> <p>Background</p> <p>Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.</p> <p>Results</p> <p>GFP-R-Ras localized to the plasma membrane, most specifically in membrane ruffles, in Cos-7 cells. GFP-R-Ras was endocytosed from these ruffles, and trafficked via multiple pathways, one of which involved large, acidic vesicles that were positive for Rab11. Cells transfected with a dominant negative form of GFP-R-Ras did not form ruffles, had decreased cell spreading, and contained numerous, non-trafficking small vesicles. Conversely, cells transfected with the constitutively active form of GFP-R-Ras contained a greater number of ruffles and large vesicles compared to wild-type transfected cells. Ruffle formation was inhibited by knock-down of endogenous R-Ras with siRNA, suggesting that activated R-Ras is not just a component of, but also an architect of ruffle formation. Importantly, ÎČ<sub>1</sub>-integrin co-localized with endogenous R-Ras in ruffles and endocytosed vesicles. Expression of dominant negative R-Ras or knock down of R-Ras by siRNA prevented integrin accumulation into ruffles, impaired endocytosis of ÎČ<sub>1</sub>-integrin, and decreased ÎČ<sub>1</sub>-integrin-mediated adhesion. Knock-down of R-Ras also perturbed the dynamics of another membrane-localized protein, GFP-VSVG, suggesting a more global role for R-Ras on membrane dynamics. However, while R-Ras co-internalized with integrins, it did not traffic with VSVG, which instead moved laterally out of ruffles within the plane of the membrane, suggesting multiple levels of regulation of and by R-Ras.</p> <p>Conclusions</p> <p>Our results suggest that integrin function involves integrin trafficking via a cycle of membrane protrusion, ruffling, and endocytosis regulated by R-Ras, providing a novel mechanism by which integrins are linked to R-Ras through control of membrane dynamics.</p
Techniques to Facilitate the Acquisition of Accurate Spectral Measurements and Multispectral Imagery of Plant Foliage Under Artificial Lighting Conditions
Spectral measurements obtained in the laboratory under artificial lighting sources have been used for many years to develop spectral âlibrariesâ for various soil types, rocks and minerals, and other inanimate features occurring on or near the earthâs surface. Quartz halogen lamps have been shown to emit all of the electromagnetic (EMR) wavelengths required for the acquisition of quality multispectral imagery, and various techniques have been developed to facilitate the acquisition of accurate spectral measurements using such artificial lighting sources. Our objectives in this study were to evaluate the several factors of critical importance in obtaining accurate spectral measurements for plant foliage in the laboratory, including the effects of leaf orientation, excision, and background reflectance on reflectance of visible and NIR wavelengths. Results demonstrated that accurate spectral measurements and imagery of various types of foliage may be obtained using quartz halogen lighting provided that excised leaf samples are placed on an NIR-absorbent background and samples are maintained in containers designed to minimize desiccation
The effect of portable HEPA filter air cleaners on indoor PM2.5 concentrations and second hand tobacco smoke exposure among pregnant women in Ulaanbaatar, Mongolia: The UGAAR randomized controlled trial
Background Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM2.5), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. Methods We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. Results The overall geometric mean (GM) one-week outdoor PM2.5 concentration was 47.9?g/m3 (95% CI: 44.6, 51.6?g/m3), with highest concentrations in winter (118.0?g/m3; 110.4, 126.2?g/m3). One-week indoor and outdoor PM2.5 concentrations were correlated (r=0.69). Indoor PM2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3?g/m3 (15.8, 18.8?g/m3) and 24.5?g/m3 (22.2, 27.0?g/m3), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. Conclusions Portable HEPA filter air cleaners can lower indoor PM2.5 concentrations and SHS exposures in highly polluted settings.Canadian Institute of Health Research (MOP 142380)Simon Fraser University, Faculty of Health Sciences (Mowafaghian Child Health Faculty Award
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes
As revealed using mice heterozygous for the base excision repair (BER) protein XRCC1, BER and mutagenic repair pathways can simultaneously compete for access to single-strand breaks induced by activation-induced deaminase
Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost
Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US15,689 versus US10,515). The average saving per patient treated with thrombectomy was US$4,365. c Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Peer reviewe
Harmful algal blooms and eutrophication : examining linkages from selected coastal regions of the United States
Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Harmful Algae 8 (2008): 39-53, doi:10.1016/j.hal.2008.08.017.Coastal waters of the United States (U.S.) are subject to many of the major harmful algal
bloom (HAB) poisoning syndromes and impacts. These include paralytic shellfish poisoning
(PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), ciguatera
fish poisoning (CFP) and various other HAB phenomena such as fish kills, loss of submerged
vegetation, shellfish mortalities, and widespread marine mammal mortalities. Here, the
occurrences of selected HABs in a selected set of regions are described in terms of their
relationship to eutrophication, illustrating a range of responses. Evidence suggestive of
changes in the frequency, extent or magnitude of HABs in these areas is explored in the
context of the nutrient sources underlying those blooms, both natural and anthropogenic. In
some regions of the U.S., the linkages between HABs and eutrophication are clear and well
documented, whereas in others, information is limited, thereby highlighting important areas
for further research.Support was provided through the Woods Hole Center for Oceans
and Human Health (to DMA), National Science Foundation (NSF) grants OCE-9808173 and
OCE-0430724 (to DMA), OCE-0234587 (to WPC), OCE04-32479 (to MLP), OCE-0138544
(to RMK), OCE-9981617 (to PMG); National Institute of Environmental Health Sciences
(NIEHS) grants P50ES012742-01 (to DMA) and P50ES012740 (to MLP); NOAA Grants
NA96OP0099 (to DMA), NA16OP1450 (to VLT), NA96P00084 (to GAV and CAH),
NA160C2936 and NA108H-C (to RMK), NA860P0493 and NA04NOS4780241 (to PMG),
NA04NOS4780239-02 (to RMK), NA06NOS4780245 (to DWT). Support was also provided from the West Coast Center for Oceans and Human Health (to VLT and WPC), USEPA
Grant CR826792-01-0 (to GAV and CAH), and the State of Florida Grant S7701617826 (to
GAV and CAH)
The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis
DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.This research was supported by USPHS grant NS073976 (TKH) and P30 ES 06676 that support the NIEHS Center Cell Biology Core and Molecular Genomics Core of UTMBâs NIEHS Center for DNA sequencing. TKP is supported by CA129537 and CA154320. This work was also supported by Fundação para a CiĂȘncia e Tecnologia through the project [PTDC/SAU-GMG/101572/2008] and through fellowships [SFRH/BPD/91562/2012 to ASF, SFRH/BD/51059/2010 to ANC]. IB is supported by NIEHS R01 ES018948 and NIAID/AI06288
CaracterĂsticas morfogenĂ©ticas e taxa de acĂșmulo de forragem do capim-Mombaça submetido a trĂȘs intervalos de pastejo
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